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Flashcards in Drug-Drug interactions Deck (27):
1

5 Rs of prescribing

- Right patient
- Right drug
- Right route
- Right time
- Right dose

2

High risk patients of drug-drug interaction

- Increases exponentially with the number of medicaments
- Elderly
- Young
- Critically ill
- Patients undergoing complicated surgical procedures
- Diseases: liver, renal, diabetes, epilepsy, asthma
- Interactions which are minor in normal patients can be really severe in other patients

3

Drug-drug interaction definition

- Modification of a drug's effect by prior or concomitant administration

4

Types of drug interactions

- Drug-drug
- Herbal-drug
- Food-drug
- Pharmacogenetic interactions

5

Characteristics of drugs likely to have a drug-drug interaction

- All these drugs are potent with a narrow therapeutic index: small change in blood levels can induce profound toxicity.
- Why it is necessary to have therapeutic drug monitoring

6

Mechanisms of drug-drug interaction: Absorption

- Formation of insoluble complexes
- Altered pH
- Altered bacterial flora
- Altered GI motility

7

How altered pH affected drug-drug interactions

- Absorption dependent on pH
- H2 antagonists, proton pump blockers (omeprazole) and antacid reduce H+ and increase the pH

8

How altered bacterial flora affected drug-drug interactions

- Usually found in the large bowel
- Broad spectrum antibiotics destroy normal gut flora
- May lead to failure of OCP or digoxin toxicity

9

How altered GI motility affected drug-drug interactions

- Complex
- Most of these interactions change absorption rate, not extent of absorption -> affects half life
- Some drugs bind to each other in GI tract: tetracycline and erythromycin complex with iron, calcium and magnesium
- Most oral medicines are absorbed in the small intestine
- Gastric emptying is rate limiting step.

10

Drugs that affect gastric emptying

- Delay emptying: anticholinergics, tricyclic, anti-depressants, opiates
- Increase gastric emptying and accelerate absorption of paracetamol: domeperidone, metoclopramide

11

Mechanisms of drug-drug interaction: Distribution

- Protein-protein placement
- Protein-binding displacement

12

How altered protein-binding displacement affected drug-drug interactions

- reduction in the extent of plasma protein binding of a drug caused by the presence of another drug
- Results in increased bioavailability of displaced drug
- Type of interaction is common but patients are protected by increased metabolism and excretion

13

Examples of protein-binding displacement drugs

- Indomethacin and warfarin
- 95% of drugs have protein binding: amitripyline, furosemide, ibuprofen
- Lithium, as an antiepileptic has the same symptoms as the disease

14

Mechanisms of drug-drug interaction: Metabolism

- Occur when one drug induces or inhibits the metabolism of another
- Through Cytochrome P450

15

Examples of drugs that inhibit cytochrome system

- Clarithromycin
- Erythromycin
- Omeprazole

16

Examples of drugs that inhibit cytochrome inducers, increase metabolism

- Carbamazepine
- Phenytoin (w/warfarin, steroids, OCP)
- Rifampicin (ciclosporin, warfarin, OCP)
- Tobacco smoke

17

Elimination

- Most drugs excreted in urine or bile
- If patient gets dehydrated, they get renal damage due to nephrotoxicity of drug, stop drinking and this changes the GFR or tubular secretion
- Have to monitor bloods and fluid intake
- Loop diuretic increase tubular reabsorption e.g. furosemide

18

Examples of toxic agents eliminated by kidney

Digoxin and lithium are examples of toxic agents eliminated by kidney

19

Pharmacodynamic drug-drug interactions

- When pharmacodynamic actions of a drug are changed due to presence of another drug either acting directly on the same receptor or indirectly on different receptors

20

Synergistic or additive drugs

- Two drugs with the same pharmacological effect acting on the same receptor are given concurrently, effect can be additive or multiplicative

21

Indirect agonism

- Central nervous system depression: Benzodiazepines and tricyclics or alcohol
- Warfarin and NSAIDs (Indomethacin)
- Atenolol and verapamil

22

Antagonistic

- Direct antagonism: beta-blockers such as atenolol will block the actions of antagonists
- Indirect antagonism: NSAIDS raise blood pressure and antihypertensives lower BP

23

Examples of pharmacodynamic drug interactions

- Synergistic or additive
- Antagonistic
- Interactions due to changes in drug transport
- Interactions due to fldui and electrolyte disturbances
- Indirect pharmacodynamic interactions

24

Object drug

Drug whose activity is affected by such an interaction

25

Precipitant

- Agent which precipitates such an interaction

26

Examples of drug interactions which are not always detrimental

- Treatment of hypertension
- Treatment of Parkinsonism with carbidopa and levidopa. Carbidopa prevents the side effects of levodopa

27

How to deal with an interaction

- Is the interaction detrimental or desired?
- Is the interaction clinically important
- Will altering the dose timing solve the interaction?
- Will using an alternative solve the interaction

If altering the timing or no alternative solve the issues then adjust the drug dosage and monitor drug level (TDM) and physiological functions